chr5-82275850-C-T

Position:

• chr5-82275850-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025.5(RPS23):​c.*259G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 436,024 control chromosomes in the GnomAD database, including 111,536 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37519 hom., cov: 32)
  • Exomes 𝑓: 0.72 (74017 hom.)
• Consequence: RPS23 NM_001025.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.61

Genes affected

RPS23 (HGNC:10410): (ribosomal protein S23) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S12P family of ribosomal proteins. It is located in the cytoplasm. The protein shares significant amino acid similarity with S. cerevisiae ribosomal protein S28. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ATG10 (HGNC:20315): (autophagy related 10) Autophagy is a process for the bulk degradation of cytosolic compartments by lysosomes. ATG10 is an E2-like enzyme involved in 2 ubiquitin-like modifications essential for autophagosome formation: ATG12 (MIM 609608)-ATG5 (MIM 604261) conjugation and modification of a soluble form of MAP-LC3 (MAP1LC3A; MIM 601242), a homolog of yeast Apg8, to a membrane-bound form (Nemoto et al., 2003 [PubMed 12890687]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS23	NM_001025.5	c.*259G>A		3_prime_UTR_variant	4/4	ENST00000296674.13	NP_001016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS23	ENST00000296674.13	c.*259G>A		3_prime_UTR_variant	4/4	1	NM_001025.5	ENSP00000296674	P1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106275 AN: 151950 Hom.: 37461 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.700

GnomAD4 exome AF: 0.717 AC: 203536 AN: 283956 Hom.: 74017 Cov.: 2 AF XY: 0.717 AC XY: 105349 AN XY: 146924

Gnomad4 AFR exome AF: 0.640

Gnomad4 AMR exome AF: 0.796

Gnomad4 ASJ exome AF: 0.629

Gnomad4 EAS exome AF: 0.950

Gnomad4 SAS exome AF: 0.738

Gnomad4 FIN exome AF: 0.681

Gnomad4 NFE exome AF: 0.697

Gnomad4 OTH exome AF: 0.701

GnomAD4 genome AF: 0.700 AC: 106391 AN: 152068 Hom.: 37519 Cov.: 32 AF XY: 0.702 AC XY: 52181 AN XY: 74328

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.772

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.703

Alfa AF: 0.704 Hom.: 61958

Bravo AF: 0.704

Asia WGS AF: 0.824 AC: 2866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs226202; hg19: chr5-81571669;